Insulin differentially regulates systemic and skeletal muscle vascular resistance

Abstract

To explore the relationships among insulin action, vascular resistance, and insulin sensitivity, we studied three groups of lean (Ln) and one group of obese (Ob) men. Glucose uptake was measured in whole body (WBGU) and in leg muscle (LGU) under basal and hyperinsulinemic euglycemic conditions. Mean arterial pressure (MAP), cardiac output (CO), leg blood flow (LBF), and systemic (SVR) and leg (LVR) vascular resistance were also ascertained. Ln groups were studied during insulin infusion rates of 20, 40, and 600 mU.m-2.min-1 and the Ob group at 40 mU.m-2.min-1. In Ob vs. Ln groups, WBGU and LGU were reduced by 51 (P < 0.01) and 42% (P < 0.05), respectively. In response to insulin, LBF increased > 60% (P < 0.01) in Ln groups but only approximately 20% in the Ob group, P = not significant (NS). CO was unchanged in Ob compared with a 15% increase (P < 0.05) in Ln groups, LBF was highly correlated with CO, r 0.70, P < 0.001. During hyperinsulinemia, MAP and LVR decreased in Ln (P < 0.001) but not in the Ob group (P = NS). In Ln groups, SVR decreased by 26 vs. 9% in the Ob group, P < 0.01. In summary, 1) insulin decreases LVR more than SVR and via this mechanism redistributes CO to insulin-sensitive tissues, 2) this insulin effect is blunted in Ob humans, and 3) insulin decreases MAP and vascular resistance more effectively in insulin-sensitive than in insulin-resistant subjects. In conclusion, insulin resistance to carbohydrate metabolism is associated with resistance to insulin's effect to decrease skeletal muscle vascular resistance and as such could act as a risk factor for the development of hypertension.